Cinnamate 4-hydroxylation

Pyrolytic Decomposition. The pyrolytic decomposition at 350—460°C of castor oil or the methyl ester of ricinoleic acid spHts the ricinoleate molecule at the hydroxyl group forming heptaldehyde and undecylenic acids. Heptaldehyde, used in the manufacture of synthetic flavors and fragrances (see Elavors and spices Perfumes) may also be converted to heptanoic acid by various oxidation techniques and to heptyl alcohol by catalytic hydrogenation. When heptaldehyde reacts with benzaldehyde, amyl cinnamic aldehyde is produced (see Cinnamic acid, cinnamaldehyde, and cinnamyl... 

By utilizing a combination of RAFT and cationic ROP, the synthesis of [poly(methyl methacrylate)][poly(l,3-dioxepane)][polystyrene] miktoarm star terpolymers was achieved [182], The approach involved the synthesis of PS functionalized with a dithiobenzoate group by RAFT polymerization and subsequent reaction with hydroxyethylene cinnamate (Scheme 98). The newly created hydroxyl group was then used for the cationic ring opening polymerization of 1,3-dioxepane (DOP). The remaining dithiobenzoate group was used for the RAFT polymerization of methyl methacrylate. 

A series of subsequent reactions after PAL first introduces a hydroxyl at the 4-position of the ring of cinnamic acid to form p- or 4-coumaric acid (i.e., 4-hydroxycinnamic acid). Addition of a second hydroxyl at the 3-position yields caffeic acid, whereas O-methylation of this hydroxyl group produces ferulic acid (see Fig. 3.3). Two additional enzymatic reactions are necessary to produce sinapic acid. These hy-drocinnamic acids are not found in significant amounts in plant tissue because they are rapidly converted to coenzyme A esters, or glucose esters. These activated intermediates form an important branch point because they can participate in a wide range of subsequent reactions. 

Cinnamate 4-hydroxylase (C4H EC 1.14.13.11, also defined as CYP73A [36]) catalyzes the p-hydroxylation of trani-cinnamate to form trani -p-coumarate. The enzyme has a requirement for molecular oxygen and NADPH as well as association with the electron donor NADPH-cytochrome P450 reductase (CPR EC 1.6.2.4) for activity. C4H was the first characterized plant P450 [37, 38]. 

The first reactions concerned (Simons and Archer, 27) alkylation of benzene with propylene to form isopropylbenzene, with isobutene to form f-butylbenzene and di-f-butylbenzene, and trimethylethylene to form amylbenzene. Later on (Simons and Archer, 28) studied these and other reactions in more detail and showed that high yields could be obtained and that the product was not contaminated with tars or other obnoxious impurities. It was shown that the products obtained with trimethylethylene were mono- and di-f-amylbenzene, that phenyl-pentane resulted from the use of pentene-2, and that cyclohexene produced cyclohexylbenzene. Cinnamic acid reacted with benzene (Simons and Archer, 29) to form /3-phenylpropionic acid and allyl benzene reacted with benzene to form 1,2-diphenylpropane. It is interesting to note that although allyl alcohol reacted with benzene to form 1,2-diphenylpropane, the intermediate in the reaction, allylbenzene, was isolated and identified. This shows that in this case the hydroxyl reacted at a more rapid rate than the double bond. Both di- and triisobutylene reacted with phenol (Simons and Archer, 30) at 0°, when using hydrogen fluoride containing only relatively small quantities of water, to form f-butyl-benzene, but diisobutylene with 70% hydrogen fluoride produced p-f-octylphenol. Cyclohexene reacted with toluene to form cyclohexyl-toluene and octene-1 rapidly reacted with toluene to form 2-octyltoluene (Simons and Basler, 31). 

The PAL activity that is necessary for lignin formation occurs in the cytoplasm or bound to the cytoplasmic surface of the endoplasmic reticulum membranes. The cinnamic acid produced is probably carried on the lipid surface of the membranes, since it is lipophilic, and it is sequentially hydroxylated by the membrane-bound hydroxylases (47,50). In this way there is the possibility of at least a two-step channeling route from phenylalanine to p-coumaric acid. The transmethylases then direct the methyl groups to the meta positions. There is a difference between the transmethylases from angiosperms and those from gymnosperms, since with the latter... 

Ferreira. Development of an HPLC/ CA090 diode-array detector method for simultaneous determination of seven hydroxyl-cinnamic acids in green coffee. J LiqChromRelTechnol 1997 20(13) CA091... 

The route to formation of flavonoids lacking 4 -hydroxylation of the B-ring has not been elucidated. However, one possible route is the direct use of cinnamate as a substrate by 4CL. Activity on cinnamate has been shown at low levels for some of the recombinant 4CL... 

Some of the pathways of animal and bacterial metabolism of aromatic amino acids also are used in plants. However, quantitatively more important are the reactions of the phenylpropanoid pathway,173-1743 which is initiated by phenylalanine ammonia-lyase (Eq. 14-45).175 As is shown at the top of Fig. 25-8, the initial product from phenylalanine is trails-cinnam-ate. After hydroxylation to 4-hydroxycinnamate (p-coumarate) and conversion to a coenzyme A ester,1753 the resulting p-coumaryl-CoA is converted into mono-, di-, and trihydroxy derivatives including anthocyanins (Box 21-E) and other flavonoid compounds.176 The dihydroxy and trihydroxy methylated products are the starting materials for formation of lignins and for a large series of other plant products, many of which impart characteristic fragrances. Some of these are illustrated in Fig. 25-8. 

Benzoic and salicylic acids. Two of the simplest plant acids arising from fraus-cinnamate are benzoic acid, accumulated in plums and cranberries, and salicylic acid, present in all green plants and accumulated as methyl esters or glycosides in some plants, e.g., those of the willow family. Salicylic acid is made by hydroxylation of benzoic acid,177 which can be formed from frans-cinnamate by P oxidation as depicted in Fig. 25-8, but it may also arise from isochoris-mate as shown in Fig. 25-2.178 Salicylic acid plays a central role in resistance of plants to a variety of... 

Compound retention during RP-HPLC depends on the relative hydrophobicity of the sample compounds. As expected, the elution of phenolics for reversed-phase HPLC is in the order of decreasing polarity. Polarity is increased most by hydroxyls at the 4-position, followed by those at the 2- and 3-positions. Availability of the methoxy group and the acrylic substitution reduces polarity and increases retention times (4). Loss of polar hydroxy groups and/or addition of methoxy groups can decrease the polarity within each class of benzoic and cinnamic acid. Also, the presence of the ethylenic side chain in the cinnamic acids can reduce their polarity compared with similarly substituted benzoic acids (6). The elution order for benzoic acids is as follows (Table 1) gallic > a-resorcylic > protocatechuic > y-resorcylic > gentisic > p-hydroxyben-... 

Isosorbide 2- and 5-nitrates substituted at the second hydroxyl group by a number of aliphatic, aromatic, and cinnamic acids (78, R = various acyl groups) have been claimed to be useful in vasodilating therapy.111 However, it was confirmed by the authors that there seems to be no direct correlation between lipophilicity and therapeutic activity, and that structure-activity relationships in the isosorbide nitrate area are more complex than that. 

Hydroxylation of aromatic rings is a very common and an important step in the biosynthesis of natural products.181,182 Arene oxides were suggested as intermediates in the biosynthesis of natural products as early as in 1967.183 However, not all hydroxylations proceed through arene oxides. A number of instances have been documented,184 as in the case of cinnamic and benzoic acids, where ortho and para hydroxylations take place by the involvement of an NIH shift (arene oxides). 

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